1. Field of the Invention
The invention relates to an aeration device for bioreactors with an aeration element with gas outlet openings.
2. Description of the Related Art
Provision of a gas supply and in particular provision of an oxygen supply is a key factor in cellular metabolic processes. Although animal cell cultures consume substantially less oxygen than bacteria and yeast cultures, ensuring an efficient supply is the greatest challenge facing the operation of a cell culture bioreactor. In addition to supplying the cells with oxygen, the concentration of dissolved carbon dioxide also plays a part as a controlled variable.
There are two conventional aeration methods: aerating the headspace of the bioreactor and direct injection of the gases through aeration rings. For this purpose, use is made not only of the aeration rings known from fermenters with bores or gas outlet openings of for example 0.8 mm but also of “microspargers” made from sintered plastics with pore sizes of for example 20 to 60 μm, which likewise form gas outlet openings. Both kinds have specific advantages and drawbacks.
The aeration ring produces larger bubbles, which means that higher gas throughput rates are required to achieve the same “oxygen transfer rate”. With its relatively large bubbles, the ring sparger is suitable for stripping or sweeping out CO2 with air, for example.
With its relatively small bubbles, the microsparger is particularly suitable for supplying oxygen.
One drawback, however, is that under unfavorable conditions foaming may occur due to the relatively small bubbles. Due to the different pore sizes of the sintered material, which inevitably form immediately spaced-apart gas outlet openings with a size of between about 20 and about 70 μm, the microsparger generates gas bubbles in a relatively wide range from about 2 mm to about 10 mm in diameter.
Aeration devices are used as part of automated bioreactor aeration systems, for example single-use reactors, the supply of air, oxygen, carbon dioxide and nitrogen being mutually independently controllable. Sensors for oxygen partial pressure and pH enable the control of these important process parameters.
WO 2009/122310 A2, WO 2009/115926 A2 and WO 2009/116002 A1 disclose single-use bioreactors with a mixer and with an aeration device arranged on the bottom of the reactor interior. It is known here to arrange two aeration elements on the bottom which take the form of opposing, mating ring segments.
Where microspargers are used for this purpose, they exhibit the above-described disadvantages.
The object of the present invention is accordingly to improve known bioreactor aeration devices taking the form of microspargers in such a manner that, while retaining a simple structure, bubble formation of the aeration element taking the form of a microsparger is enabled in a more narrowly and better definable range.